T Cell Cytokines as Immunomodulators of Arthritis Disease Pathology
Thomas F. Kresina in Monoclonal Antibodies, Cytokines, and Arthritis, 2020
In addition to the interleukins, other cytokines may mediate the inflammation of arthritis. Several hematopoietic growth factors have been reported to be present in the synovial fluid of rheumatoid arthritis patients. Granulocyte-macrophage colony stimulating factor (127), macrophage colony-stimulating factor (110), and a mast cell growth factor have been found to be present in increased amounts in the synovial fluids of patients with inflammatory arthritis. The role of these cytokines in rheumatoid arthritis is not understood at this time, but it is likely that they are involved in the modulation of the immune response. For example, granulocyte-macrophage colony stimulating factor increases Ia expression and the secretion of interleukin-1 in murine macrophages (128). The modulation of interleukin-1 secretion by this cytokine could be important in the modulation of the inflammatory response observed in arthritis.
Immunomodulators: What is the evidence for use in mycoses?
Mahmoud A. Ghannoum, John R. Perfect in Antifungal Therapy, 2019
Mature human leukocytes differentiate from precursor cells in response to colony stimulating factors (CSFs). Granulocyte colony-stimulating factor (G-CSF) increases the number of mature neutrophils by increasing the production of these cells and by inhibiting apoptosis [29]. Clinically, G-CSF has played a major role in the treatment of many hematological disorders. This cytokine reduces the period of neutropenia after chemotherapy, resulting in reduced hospitalizations and antimicrobial use [30,31]. Also, G-CSF therapy has allowed the transplantation of hematopoietic stem cells instead of bone marrow cells for recovery after marrow ablative therapy. Similarly, GM-CSF (granulocyte-macrophage colony-stimulating factor) and M-CSF (macrophage colony-stimulating factor) promote the maturation of granulocytes/macrophages or macrophages, respectively [32].
Pathogenesis of Tuberculosis
Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies in Clinical Tuberculosis, 2020
Although the mechanism by which CD4 and CD8T cells protect mice against subsequent challenge with MTB still is not totally clear, studies indicate that there are two potential mechanisms for protection. Secretion of macrophage-activating cytokines such as IFN-γ, and possibly other molecules such as granulocyte−macrophage colony stimulating factor, induces MTB growth inhibition within macrophages. Studies using mice with genetic disruption of IFN-γ have shown the absolute necessity for this TH-1 cytokine in the control of MTB infection.137,138 The other mechanism by which T cells may be protective is by cytotoxicity for mycobacterial-laden macrophages. Thus, class I MHC dysfunctional mice were more susceptible to MTB infection.139 However, mice with genetic disruption of perforin, a molecule involved in CD8 cytotoxicity, did not demonstrate enhanced susceptibility to MTB infection.140 Current thinking is that the IFN-γ/IL-12 axis is critical to protection. IL-12 is produced early in infection by Ag-presenting cells, and promotes the differentiation of T-helper cells and production of IFN-γ. IFN-γ further activates macrophages to produce TNF-α and other protective cytokines that promote intracellular killing of MTB.
Immunological mechanisms underlying sterile inflammation in the pathogenesis of atherosclerosis: potential sites for intervention
Published in Expert Review of Clinical Immunology, 2021
Roland Truong, Finosh G. Thankam, Devendra K. Agrawal
Within the intima layer, ox-LDL acts as a ligand and interacts with scavenger receptors, SR-A1 and CD36 which are expressed on macrophages [18,19]. Subsets of monocytes have been identified and classified based on cell surface epitope recognition using flow cytometry as classical (CD14high/CD16−), intermediate (CD14high/CD16+), and non-classical (CD14low/CD16+) in humans [20]. The ‘intermediate’ monocytes which express high levels of CD14 and intermediate CD16 (CD14high/CD16+) have been associated with cardiovascular death, myocardial infarction, and death [21,22]. In response to macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) released from endothelial cells, the monocytes differentiate into macrophages [23]. Binding of ox-LDL with scavenger receptors, SR-A1 and CD36, results in further activation of macrophages and uptake of ox-LDL. Macrophages within the tunica intima layer uptake ox-LDL and form foam cells leading to lipid-rich plaque. The plaque includes other inflammatory cells that forward a cascade of immune response leading to vulnerability of the fibrous cap, eventual rupture, and thrombotic events [11,24].
Alzheimer’s disease: microglia targets and their modulation to promote amyloid phagocytosis and mitigate neuroinflammation
Published in Expert Opinion on Therapeutic Targets, 2020
On the other hand, there is clear evidence that a robust inflammatory response of microglia is not necessary to increase its phagocytic efficacy [16]. For instance, macrophage colony-stimulating factor (M-CSF) enhances the phagocytosis of Aβ with minimal pro-inflammatory activities [17]. Similarly, phagocytosis of apoptotic neurons mediated by microglial triggering receptor expressed on myeloid cells-2 (TREM-2) was associated with decreased production of pro-inflammatory cytokines [18]. Likewise, stimulation of nicotinic acetylcholine receptors (nAChRs) on microglia dramatically promotes Aβ phagocytosis and improves cognitive impairment in a mouse model of AD [19,20]. Additionally, nicotine treatment suppresses the microglia pro-inflammatory responses [21]. Accordingly, finely tuned activation of microglia in a particular direction, which is a potent phagocytic potential with a low inflammatory response could be a possible therapeutic approach against AD [22].
The Goiânia incident, the semiotics of danger, and the next 10,000 years
Published in Clinical Toxicology, 2023
Joseph Clemons, Adam Blumenberg
Observations from serial bone marrow aspirates and biopsies corresponded with changes in granulocyte concentrations. The granulocyte recovery kinetics demonstrated a marked difference between treated and untreated individuals. Moreover, the application of granulocyte-macrophage colony-stimulating factor did not appear to influence the recovery of red blood cells or platelets. Four out of eight patients treated with granulocyte-macrophage colony-stimulating factor survived, with the fatalities being patients colonized with gram-negative bacteria prior to the initiation of granulocyte-macrophage colony-stimulating factor treatment. The side effects of granulocyte-macrophage colony-stimulating factor treatment were generally mild. Some instances of respiratory failure and/or pulmonary edema were reported during therapy, predominantly in patients with bacterial sepsis. Although these episodes were primarily attributed to infection, an effect of granulocyte-macrophage colony-stimulating factor could not be definitively excluded. Both patients who exhibited spontaneous hematological recovery survived, with one requiring forearm amputation due to severe radiation burns [15].
Related Knowledge Centers
- Colony Stimulating Factor 1 Receptor
- Parathyroid Hormone
- Placenta
- Hematopoietic Stem Cell
- Endocrine System
- Cytokine
- Macrophage
- Colony-Stimulating Factor
- Monocyte
- Osteoblast